title: Phosphorylation state of Olig2 regulates proliferation of neural progenitors.
abstract: The bHLH transcription factors that regulate early development of the central nervous system can generally be classified as either antineural or proneural. Initial expression of antineural factors prevents cell cycle exit and thereby expands the pool of neural progenitors. Subsequent (and typically transient) expression of proneural factors promotes cell cycle exit, subtype specification, and differentiation. Against this backdrop, the bHLH transcription factor Olig2 in the oligodendrocyte lineage is unorthodox, showing antineural functions in multipotent CNS progenitor cells but also sustained expression and proneural functions in the formation of oligodendrocytes. We show here that the proliferative function of Olig2 is controlled by developmentally regulated phosphorylation of a conserved triple serine motif within the amino-terminal domain. In the phosphorylated state, Olig2 maintains antineural (i.e., promitotic) functions that are reflected in human glioma cells and in a genetically defined murine model of primary glioma.
authors.affiliation: Department of Cancer Biology, Harvard Medical School and Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Dimphna H
authors.initials: DH
authors.lastname: Meijer
authors.forename: John A
authors.initials: JA
authors.lastname: Alberta
authors.forename: Shwetal
authors.initials: S
authors.lastname: Mehta
authors.forename: Michael F
authors.initials: MF
authors.lastname: Kane
authors.forename: An-Chi
authors.initials: AC
authors.lastname: Tien
authors.forename: Hui
authors.initials: H
authors.lastname: Fu
authors.forename: Magdalena A
authors.initials: MA
authors.lastname: Petryniak
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Potter
authors.forename: Zijing
authors.initials: Z
authors.lastname: Liu
authors.forename: James F
authors.initials: JF
authors.lastname: Powers
authors.forename: I Sophie
authors.initials: IS
authors.lastname: Runquist
authors.forename: David H
authors.initials: DH
authors.lastname: Rowitch
authors.forename: Charles D
authors.initials: CD
authors.lastname: Stiles
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015153:Blotting, Western; D019070:Cell Lineage / Q000502:physiology; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C405708:OLIG2 protein, human